Nb-induced stabilisation of p53 in HPV-infected cells.

ABSTRACT: Cervical cancer is caused by a persistent infection of the mucosal epithelia with high-risk human papilloma viruses (HPVs). The viral oncoprotein E6 is responsible for the inactivation of the tumour suppressor p53 and thus plays a crucial role in HPV-induced tumorigenesis. The viral E6 protein forms a trimeric complex with the endogenous E3 ubiquitine ligase E6AP and the DNA-binding domain (DBD) of p53, which results in the polyubiquitination and proteasomal degradation of p53. We have developed nanobodies (Nbs) against the DBD of p53, which substantially stabilise p53 in HeLa cells. The observed effect is specific for HPV-infected cells, since similar effects were not seen for U2OS cells. Despite the fact that the stabilised p53 was strongly nuclear enriched, its tumour suppressive functi

SUBMITTER: Steels A 

PROVIDER: S-EPMC6722090 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature